Left iliac vein involvement is a protective factor against symptomatic pulmonary embolism in lower left extremity deep vein thrombosis.

OBJECTIVE: Left iliac vein compression is associated with left iliac vein thrombosis (IVT), potentially limiting the migration of the thrombus from this stenotic segment to the pulmonary arteries. We sought to investigate the differences in clinical characteristics and risk factors of symptomatic pulmonary embolism (SPE) in patients with deep vein thrombosis (DVT) in different limbs and anatomical locations. METHODS: A retrospective analysis was conducted of 1476 patients with acute unilateral lower extremity DVT. Differences of clinical characteristics and risk factors between left-sided and right-sided DVT, IVT, and non-IVT, cases with SPE and cases without SPE were compared. Risk factors for SPE were investigated using logistic regression analysis. RESULTS: SPE was more common in patients with right-sided DVT than patients with left-sided DVT (13.8% vs 7.0%; P < .001). SPE incidence in left IVT (5.4%) was lower than that in left non-IVT, right IVT, and right non-IVT (12.8%, 10.1%, 16.6%, respectively; P < .001). There was no difference in SPE incidence among patients with left non-IVT, right IVT and right non-IVT (P > .05). In patients with left-sided DVT, male sex was associated with an increased odds of SPE (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.10-2.85; P = .02). IVT, surgery, and immobilization were associated with a decreased odds of SPE (OR, 0.46 [95% CI, 0.28-0.76; P < .01]; OR, 0.55 [95% CI, 0.32-0.95; P = .03]; and OR, 0.53 [95% CI, 0.32-0.86; P = .01]). In patients with right-sided DVT, provoked DVT was associated with a decreased odds of SPE (OR, 0.50; 95% CI, 0.27-0.93; P = .03). CONCLUSIONS: Left IVT is associated with a lower SPE incidence than right-sided DVT. Left IVT and may be a relative protective factor against SPE.

Targeting Non-Genomic Activity of Retinoic Acid Receptor-Gamma by Acacetin.

Retinoic acid receptors (RARs) are ligand-dependent transcription factors of nuclear hormone receptor superfamily (NR). They are important pharmacological targets and current drug development paradigms are largely based on their nuclear transcription mechanism (genomic action). However, the side effects and limited therapeutic efficacy of retinoid-like drugs with such strategy remain a problem in clinical practice. Increasing evidences have demonstrated that many NRs including RARs can act outside the nucleus in a transcription-independent manner (non-genomic action), which are often implicated in human pathological conditions, suggesting that targeting to the non-genomic signaling of NRs is an alternative method for drug discovery. We recently reported that acacetin could antagonize the non-genomic action of RARγ via tipping the balance of AKT-p53 driven by RARγ from tumor promoting to tumor suppressive effect. This chapter provides methodology for identification of acacetin as a ligand and regulator of non-genomic signaling of RARγ. These laboratory protocols should be helpful for those researchers and beginners who are passionate about identifying chemical leads to probe the non-genomic roles of RARs and other NRs for developing new therapeutic technologies.

Left iliac vein compression is not associated with infrainguinal deep venous thrombosis but is associated with iliac vein involvement.

OBJECTIVE: The purpose of this study was to investigate whether left iliac vein (LIV) compression had similar correlation with the risk of left iliac deep venous thrombosis (DVT; iliac vein involvement) and infrainguinal DVT (without iliac vein involvement). METHODS: A retrospective analysis of records and enhanced computed tomography images was conducted of 278 patients with left-sided DVT (iliac DVT, 228 patients; infrainguinal DVT, 50 patients) and 232 control patients without DVT on either side. The influences of LIV compression on the risk of left iliac DVT and infrainguinal DVT were investigated using logistic regression analysis. RESULTS: Mean percentage compression of the LIV in left iliac DVT (74.64% ± 0.99%) patients was significantly higher than in non-DVT patients (53.42% ± 1.49%; P < .01). However, mean percentage compression of the LIV in left infrainguinal DVT patients (45.37% ± 2.71%) was significantly lower than in non-DVT patients (53.42% ± 1.49%; P < .01). LIV compression was associated with increased odds of left iliac DVT (odds ratio, 1.88; 95% confidence interval, 1.64-2.15; P < .01) for each 10% increase in percentage compression of the LIV. However, LIV compression was not associated with increased odds of infrainguinal DVT (odds ratio, 0.89; 95% confidence interval, 0.76-1.03; P = .126). CONCLUSIONS: Left iliac DVT patients had more severe LIV compression than left infrainguinal DVT patients did. LIV compression was not associated with development of left infrainguinal DVT, but it did correlate with the presence of left-sided DVT with iliac vein involvement.

Targeting to the non-genomic activity of retinoic acid receptor-gamma by acacetin in hepatocellular carcinoma.

We recently demonstrated that retinoic acid receptor-γ (RARγ) is overexpressed and acts as a tumor promoter in hepatocellular carcinoma (HCC). The oncogenic activity of RARγ is mainly attributed to its physiological interaction with p85α regulatory subunit of PI3K leading to constitutive activation of AKT. Here we report RARγ as a negative regulator of p53 signaling and thus extend the oncogenic potential of RARγ to a new role in controlling the balance between AKT and p53. A natural flavonoid acacetin is then identified to be capable of modulating RARγ-dependent AKT-p53 network. It specifically binds to RARγ and inhibits all-trans retinoic acid (atRA) stimulation of RARγ transactivation. However, the anticancer action of acacetin is independent on its modulation of RARγ-driven transcriptional activity. Acacetin induces cancer cell apoptosis through antagonizing the non-genomic effect of RARγ on AKT and p53. When bound to RARγ, acacetin prevents RARγ from its activation of AKT followed by recovery of the normal p53 signaling. Given the implication of AKT-p53 dysregulation in most HCC, targeting the non-genomic signaling of RARγ that switches AKT-p53 from a pro-survival to a pro-apoptotic program in cancer cells should be a promising strategy for developing novel anti-HCC drugs.

In vitro evaluation of antiviral activity of tea seed saponins against porcine reproductive and respiratory syndrome virus.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major swine pathogens. This virus causes immune suppression and other secondary infections, leading to significant economic losses in the swine industry. Tea seed saponins (TS) are a natural extract from tea seeds with anti-cancer, anti-inflammatory and antiviral activity. In this study, we demonstrated that TS possessed anti-PRRSV activity. METHODS: MTT assay and trypan blue staining were used to evaluate the cytotoxicity and antiviral ability of TS in cell culture. Apoptosis was measured to assess the safety of TS on Marc-145 cells. Time-of-addition assay, entry inhibition assay and virucidal assay were used to assess the antiviral action of TS. The effect of TS on host cellular gene expression was analysed by real-time PCR. Absolute quantification RT-PCR and western blot were used to study the inhibitory effect of TS on PRRSV N gene and protein expression. RESULTS: Our results showed that 50% cytotoxic concentrations (CC50) and 50% effective concentration (EC50) of TS were 59.86 ±0.3841 µg/ml and 24.29 ±1.194 µg/ml, respectively. The maximum non-cytotoxic concentration of TS on Marc-145 cells was 30 µg/ml. TS inhibited PRRSV-induced cell apoptosis and effectively inhibited PRRSV replication by reducing the expression of host cellular gene PABP, and significantly inhibited virus N gene/protein expression. CONCLUSIONS: TS possessed anti-PRRSV activity in vitro and could serve as a potential antiviral drug for PRRSV prevention and control.

[The relationship between association of microalbuminuria and retinal vessel diameter in population with essential hypertension].

OBJECTIVE: To investigate the association of urinary albumin-to-creatinine ratio (UACR) and the diameter of retinal vessel in population with essential hypertension in Fujian coastal area. METHODS: Central retinal artery and vein equivalents (CRAE and CRVE) were measured from the avoiding mydriatic digitized photographs and semi-automatic fundus analysis software, as well as albumin and urine creatinine. RESULTS: There were significant differences in CRAE levels among the normal control group, normoalbuminuria with essential hypertension group and microalbuminuria with essential hypertension group [(135.68 ± 10.10) µm, (129.79 ± 10.48) µm, (125.29 ± 11.17) µm, all P values < 0.01]. The CRAE levels were significantly negative correlated with UACR (r = -0.29, P < 0.01). Linear regression analysis showed CRAE was associated with UACR in the patients with hypertension(ß = -5.0, P < 0.01). Logistic regression analysis showed, systolic blood pressure (ß = 1.08, P = 0.02) was risk factor for CRAE abnormality. The CRAE abnormality was increased in turn in the normal control group, normoalbuminuria with the essential hypertension group and microalbuminuria with essential hypertension group (P < 0.01). CONCLUSION: The reduction of central retinal artery diameter are associated with the hypertensive renal damage. UACR and CRAE could be used to evaluate the microvascular lesions and be used as an indicator to assess the target organs damage in essential hypertension patients.